The proposed research deals with theoretical and experimental work related to three areas of experimental cardiology: (1) Mechanisms of pacemaker synchronization in the sinoatrial node; (2) Impulse conduction across nonhomogeneous tissues; and (3) Vagal control of heart rate and AV conduction. First, we wish to use the sucrose gap technique in a study of the electrophysiologic mechanisms involved in the synchronous firing of sinoatrial pacemakers at various degrees of intercellular coupling. The results of these experiments will be used for computer simulations of higher order interactions and mutual entrainment of sinoatrial pacemaker cells in situ. Second, we will develop a model of the AV conducting system. We will employ a sucrose gap preparation of Purkinje tissue or ventricular muscle trabeculae to mimic the conditions of nonhomogeneity in functional areas of the AV node, and to study frequency dependent alterations of AV conduction as well as the cellular mechanisms of some forms of supraventricular tachycardias. Finally, in isolated vagus-SA node-AV node preparations, we will study the dynamic parasympathetic control of the two nodal systems. One group of these experiments will be designed to test the hypothesis that the secondary phase of vagal inhibition of sinoatrial pacemaker activity results from the release of activation of a secondary mediator, possibly cyclic GMP. In a second group, we will study the alterations in sinoatrial pacemaker activity and AV conduction that result from periodic vagal discharge. The results of these experiments will be used to program a computer in a mathematical model of the dynamic vago-nodal interactions.